Clinical Scenario:
A woman with phenylketonuria becomes pregnant but does not adhere to her phenylalanine-restricted diet. Her plasma phenylalanine remains markedly elevated throughout pregnancy. She gives birth to an infant who has normal phenylalanine metabolism and does not have phenylketonuria.
Which of the following abnormalities is the infant most likely to have?
A. Congenital hypothyroidism
B. Cystic fibrosis
C. Microcephaly and congenital heart disease
D. Neonatal hypoglycemia
E. Renal agenesis
Correct answer & Explanation:
Answer: C. Microcephaly and congenital heart disease
Explanation
This is maternal phenylketonuria (maternal PKU) syndrome. It results from the teratogenic effects of markedly elevated maternal phenylalanine, which readily crosses the placenta and can damage the developing fetus.
The major fetal complications include:
- Microcephaly
- Intellectual disability
- Intrauterine growth restriction
- Congenital heart disease
Importantly, these complications can occur even when the fetus does not inherit PKU. The problem is exposure to high maternal phenylalanine during pregnancy rather than phenylalanine accumulation caused by the infant’s own metabolic defect.
Strict phenylalanine control before conception and throughout pregnancy markedly reduces the risk of maternal PKU syndrome.
Exam pearl:
Maternal PKU + poor dietary control → high maternal phenylalanine → fetal microcephaly + intellectual disability + growth restriction + congenital heart disease.
